A major problem in the treatment of obesity is the lack of success in maintaining the reduced obese (RO) patient at appropriate weight. There is evidence that the tendency to retain weight is caused, in part by the hypometabolic status of these individuals when in the weight-reduced state. Many characteristics of hypothalmic, thyroid, and sympathetic autonomic function in weight stable RO resemble those of fasting individuals. As a mechanism for these changes, we propose that the relative preponderance of sympathetic autonomic tone/receptivity is shifted from beta (energy releasing) to alpha (energy conserving) in certain RO, resulting in a fasting-like metabolic state, despite stable weight. The human studies described in this proposal are designed to examine endocrinologic, metabolic and psychophysical reflections of sympathetic autonomic function in obese, normal and RO individuals. These include: (1) anterior pituitary hormone release to various stimuli; (2) measurements of plasma insulin, glycerol and free fatty acid responses to graded epinephrine infusions; (3) in-vitro assessment of relative alpha/beta adrenergic receptor status in adipose tissue aspirates using an extremely sensitive dual radioisotope technique; (4) determination of plasma T3 and systemic energy consumption (by indirect calorimetry as well as long-term caloric intake measurement); (5) assessment of hypothalamic thermoregulatory function; (6) examination of pharmacologic agents (phentolamine,1-Dopa), hormones (T3), and aerobic exercise for their effects on the symptoms and metabolic-endocrine dysfunction engendered by preponderance of alpha adrenergic activity. While these studies are clearly of direct clinical relevance, they will also generate important data in man regarding the basic physiology of energy metabolism, autonomic influences on hypothalamic-pituitary interactions, the comparability of various in-vitro and in-vivo measures f catechol responsivity, and sensitivity of these measures to pharmacologic and hormonal manipulation.